title: Dextromethorphan as a potential rapid-acting antidepressant.
abstract: Dextromethorphan shares pharmacological properties in common with antidepressants and, in particular, ketamine, a drug with demonstrated rapid-acting antidepressant activity. Pharmacodynamic similarities include actions on NMDA, μ opiate, sigma-1, calcium channel, serotonin transporter, and muscarinic sites. Additional unique properties potentially contributory to an antidepressant effect include actions at ß, alpha-2, and serotonin 1b/d receptors. It is therefore, hypothesized that dextromethorphan may have antidepressant efficacy in bipolar, unipolar, major depression, psychotic, and treatment-resistant depressive disorders, and may display rapid-onset of antidepressant response. An antidepressant response may be associated with a positive family history of alcoholism, prediction of ketamine response, increased AMPA-to-NMDA receptor activity ratio, antidepressant properties in animal models of depression, reward system activation, enhanced erythrocyte magnesium concentration, and correlation with frontal μ receptor binding potential. Clinical trials of dextromethorphan in depressive disorders, especially treatment-resistant depression, now seem warranted.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31201, USA. eclbgnp@earthlink.net
authors.forename: Edward C
authors.initials: EC
authors.lastname: Lauterbach
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003865:Major Depressive Disorder / Q000188:drug therapy*; D003915:Dextromethorphan / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D011950:Receptors, Cholinergic / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists; D011985:Receptors, Serotonin / Q000378:metabolism; D017480:Receptors, sigma / Q000819:agonists; D000097605:Sigma-1 Receptor
chemical_list: D000928:Antidepressive Agents; D002121:Calcium Channel Blockers; D003915:Dextromethorphan; D018691:Excitatory Amino Acid Antagonists; D011950:Receptors, Cholinergic; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor